Ultrasound contrast agents used for enhancement of ultrasonic images have gone through several generations of development (Postema et al., 2006, Expert. Rev. Mol. Diag. 6:493-501). The common feature is a gas core plus a stabilizing shell. First-generation agents comprised air plus a shell of albumin, lipid, or acrylate. Second-generation agents improved upon the first-generation by employing gases other than air, typically fluorinated compounds (octafluoropropane, perfluorobutane, or sulfur hexafluoride). Owing to lower solubility in water and slower diffusivity of these gases relative to air, microbubbles produced from these gases were more long-lived than their first-generation counterparts. Third-generation agents built upon the second-generation agents by incorporating into the stabilizing shell a species that conveys added stability (e.g., charged surfactants or PEGylated lipids to prevent microbubble coalescence) or targets a specific receptor within tissue (via receptor ligands, analogous to avidin-biotin binding). More recent research activity has involved design of microbubbles along similar lines but for the purpose of targeted or controlled drug delivery, rather than for imaging (Lum et al., 2006, J. Control Release 111:128-134; Klibanov et al., 1994, Adv. Drug Deliv. Rev. 37:139-157; Kheirolomoom et al., 2007, J. Control Release 118:275-284; Unger et al., 2002, Eur. J. Radiol. 42:160-168).
There is a long felt need in the art for novel compositions with unique properties that may act as both superior ultrasound contrast agents and targeted drug delivery vehicles. The present invention fulfills this need.